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Maintained gamma band activity is a key element of higher brain function, participating in perception, executive function, and memory. The pedunculopontine nucleus (PPN), as part of the reticular activating system (RAS), is a major source of the "bottom-up" flow of gamma activity to higher regions. However, interruption of gamma band activity is associated with a number of neurological and psychiatric disorders. This review will focus on the role of the PPN in activating higher regions to induce arousal and descending pathways to modulate posture and locomotion. As such, PPN deep brain stimulation (DBS) can not only help regulate arousal and stepping, but continuous application may help maintain necessary levels of gamma band activity for a host of other brain processes. We will explore the potential future applications of PPN DBS for a number of disorders that are characterized by disturbances in gamma band maintenance.

The pedunculopontine nucleus (PPN), part of the reticular activating system, modulates waking and paradoxical sleep. During waking and paradoxical sleep, EEG responses are characterized by low-amplitude, high-frequency oscillatory activity in the beta–gamma band range (20–80 Hz). We have previously reported that gamma band activity may be intrinsically generated by the membrane electroresponsiveness of PPN neurons, and that the neuronal ensemble generates different patterns of gamma activity in response to specific transmitters. This study attempted to identify the voltage-gated calcium and potassium channels involved in the rising and falling phases of gamma oscillations in PPN neurons. We found that all rat (8–14 day) PPN cell types showed gamma oscillations in the presence of TTX and synaptic blockers when membrane potential was depolarized using current ramps. PPN neurons showed gamma oscillations when voltage-clamped at holding potentials above )30 mV, suggesting that their origin may be spatially located beyond voltage-clamp control. The average frequency for all PPN cell types was 23 ± 1 Hz and this increased under carbachol (47 ± 2 Hz; anova df = 64, t = 12.5, P < 0.001). The N-type calcium channel blocker x-conotoxin-GVIA partially reduced gamma oscillations, while the P ⁄ Q-type blocker x-agatoxin-IVA abolished them. Both x-CgTX and x-Aga blocked voltage-dependent calcium currents, by 56 and 52% respectively. The delayed rectifier-like potassium channel blocker a-dendrotoxin also abolished gamma oscillations. In carbachol-induced PPN population responses, x-agatoxin-IVA reduced higher, and x-CgTx mostly lower, frequencies. These results suggest that voltage-dependent P ⁄ Q- and, to a lesser extent, N-type calcium channels mediate gamma oscillations in PPN. Fil: Kezunovic, Nebojsa. University Of Arkansas For Medical Sciences; Estados Unidos Fil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Simon, Christen. University Of Arkansas For Medical Sciences; Estados Unidos Fil: Hyde, James. University Of Arkansas For Medical Sciences; Estados Unidos Fil: Smith, Kristen. University Of Arkansas For Medical Sciences; Estados Unidos Fil: Garcia Rill, E.. University Of Arkansas For Medical Sciences; Estados Unidos

This issue is dedicated to a potential new target for the treatment of movement disorders, the pedunculopontine tegmental nucleus (PPTg), or, more simply, the pedunculopontine nucleus, that some authors abbreviate as PPN. We provide an overview of the field as an introduction to the general reader, beginning with the clinical experience to date of Mazzone and co-workers in Rome, some basic questions that need to be addressed, and potential future directions required in order to ensure that the potential benefits of this work are realized.